Many main agents contained in capsules or medicines are badly affected by pH, degrading enzyme. Especially, they are orally administrated in a human passing through digestive organs in the human body and are degraded by a secretion (such as stomach acid, bile acid, pepsin, lipase and the like). It is very important for fields of medicine or functional food that such main agent is safely conveyed to an targeted portion of a human body without any degradation.
Hitherto there have been many patent applications, such as JP-A-7-2650, JP-A-7-10745, JP-A-4-41422, JP-A-4-225922, JP-A-10-324642, JP-A-2001-48779, JP-A-2011-105654, JP-A-7-2701, JP-A-6-179618, JP-A-01/10467 and JP-A-7-69867 that describe a medicine that is coated for release in the intestine.
JP-A-7-2650 and JP-A-7-10745 disclose a combination of a release-controlled medicine and an intestine-soluble coating, whereby the medicine is released after passing through a stomach in which strong acid attacks the medicine. In the technique of Patent Documents, variation of release starting times is controlled to some degree, in comparison with a medicine not having an intestine-soluble coating, but release starting times are still varied based on differences of body conditions among individuals.
JP-A-4-41422, JP-A-4-225922, JP-A-10-324642, JP-A-2001-48779 and JP-A-2011-105654 disclose that a medicine content is covered with a chitosan coating and then the chitosan coating is further covered with an intestine-soluble coating which is resistant to stomach acid. The chitosan coating is disintegrated in large intestine by action of enteric microbes or osmotic pressure to release the medicine content in large intestine. Chitosan generally does not dissolve in water or organic solvent but dissolves only in acid solution. When producing the chitosan coating, chitosan should be dissolved in acid solution and the medicine content should be covered with the chitosan acid solution. However, the chitosan coating should include acid in a small amount and can not cannot exclude acid completely. The presence of acid in the chitosan coating lowers acid resistance of the coating and may lead bad effects on the content inside the chitosan coating.
JP-A-7-2701 proposes use of water soluble chitosan having a deacetylation degree of 40 to 60%, in order to solve the problem of using acid for dissolving chitosan. The water soluble chitosan does not have enough water resistance and is not suitable for materials which specifically disintegrate in large intestine.
JP-A-6-179618 proposes a process for producing a chitosan-cured capsule, which comprises dissolving chitosan in an acid solution in which silica microparticles are dispersed, and forming it to a suitable shape by drying and solidifying, followed by treating it with alkali to remove acid residue, in order to solve the problem of using acid for dissolving chitosan. However, for actually conducting the process, additional process (e.g. rinsing the resulting capsules with water to remove excess alkali and salt as side products) is necessary together with the alkali treatment.
JP-A-01/10467 proposes that a content is covered with a water-insoluble polymer in which chitosan powder is dispersed, followed by covering it with intestine-soluble polymer (i.e. hydrophobic polymer), in order to solve the problem of using acid for dissolving chitosan. Since organic solvent is necessary for dissolving the hydrophobic polymer, the use of organic solvent necessitates safety in producing procedure and leads other problems, such as removal of organic solvent, adverse effects on the content of the capsule and enhance of production cost.
The present inventors proposed an intestine-soluble capsule of which a shell is formed from a mixture of gelatin as natural water-soluble polymer and pectin (see Patent Document 11). However, the capsule is not large intestine soluble. Capsules which disintegrate specifically in large intestine are still desired.